Cancer metastasis is strongly correlated with a poor prognosis of patients. The multi-step process of metastasis includes release of malignant cells from the primary neoplasm, migration of cancer cells into circulation, adhesion at distant sites, and growth of the disseminated cancer cells within the vessels or within the tissue following extravasation. Each step in this process requires different types of interaction between cancer cells and the host microenvironment.
The selectin family of adhesion molecules include P-Selectin, L-Selectin, and E-Selectin. P-Selectin is a 140 kDa protein that is commonly expressed on the surface of a variety of cell types, including, but not limited to, platelets and endothelium. (See, for example, GenBank Accession No. P16109 (Homo sapiens) or GenBank Accession No. AAA40008 (Mus musculus).) E-Selectin is commonly expressed in a variety of cell types, including, for example, vascular endothelium. (See, for example, NP—000441 (Homo sapiens) or AAA37577 (Mus musculus).) L-selectin is expressed on lymphocytes.
Cell surface proteoglycans (PGs) are another class of cell surface adhesion molecules. These PGs may comprise glycosaminoglycan (GAG) side chains covalently bound to a protein core. The GAG side chain can be heparin sulfate (HS) or chondroitin sulfate (CS).
The mammary cell line 4T1 is a model system of spontaneous breast cancer metastasis. This model exhibits a deficiency in the oligosaccharides sialyl Lewis X (sLex) and sialyl Lewis A (sLea). This deficiency results in diminished homotypic adhesion and higher motility of the tumor cells.